Luteal phase support (LPS): dose ranging issues and new perspectives

Transcription

1 Charlers Chapron Bruno Borghese Hervé Foulot Amin Bititi Paul Mazurk Guillaume Pierre Marie Christine Lafay Fouzia Decupere François X. Aubriot Dominique de Ziegler Vanessa Gayet Pietro Santulli Rebecca Monffat Paul Pitrea Corine Menez Bander Kuttbi Ann Marszalek Alessandra Fubini

2 The needs for LPS The options existing and doses used A sub-cutaneous P4 preparation Non-pelvic effects of P4?

3 The needs for LPS The options existing and doses used A sub-cutaneous P4 preparation Non-pelvic effects of P4?

4 Defective luteal support in ART due to high hormone levels, GnRH analogues and hcg.

5 On retrieval day or the day after, for minimizing UC at time of transfer. Earlier onset may advance closure of window of receptivity

6 On retrieval day or the day after, for minimizing UC at time of transfer. Earlier onset may advance closure of window of receptivity

7 On retrieval day or the day after, for minimizing UC at time of transfer. Earlier onset may advance closure of window of receptivity

8 On retrieval day or the day after, for minimizing UC at time of transfer. Earlier onset may advance closure of window of receptivity At time of luteo-placental shift or as early as the time of the positive pregnancy test.

9 The needs for LPS The options existing and doses used A sub-cutaneous P4 preparation Non-pelvic effects of P4?

10 Parenteral Oral Transdermic Vaginal First described Poor bioavailability Poor permeability

11 P4 Oral P4: Not efficacious due to hepatic metabolism Trans dermal P4: Not possible due to quantities (25mg/day) and skin metabolism IM SC

12 P4 Oral P4: Not efficacious due to hepatic metabolism IM SC P4 vaginal Trans dermal P4: Not possible due to quantities (25mg/day) and skin metabolism Vaginal P4: The only practical alternative to IM P4 first uterine pass effect

13 vag IM Serum levels P vag IM Uterine tissue IM vs. vaginal No differences: why? Oral P4: Not efficacious due to hepatic metabolism P4 IM SC vaginal Trans dermal P4: Not possible due to quantities (25mg/day) and skin metabolism Vaginal P4: The only practical alternative to IM P4 first uterine pass effect

14 vag IM Serum levels P vag IM Uterine tissue IM vs. vaginal No differences: why? P4 IM SC vaginal first uterine pass effect

15 Parenteral First described 5/5/13

16 Vaginal

17 Doses

18 Doses

19 Doses Hormone: P4

20 The needs for LPS The options existing and doses used A sub-cutaneous P4 preparation Non-pelvic effects of P4?

21 Parenteral Oral Transdermic Vaginal First described Poor bioavailability Poor permeability

22 New self-injectable P4 (25mg/d) Transdermic Vaginal cyclodextrin

23 cyclodextrin New self-injectable P4 (25mg/d)

24 New self-injectable P4 (25mg/d) & 50mg: 100% decidua-lized endomrium No difference between the 2 doses tested cyclodextrin de Ziegler et al. Fertil Steril 2013

25 Progesterone ng/ml New self-injectable P4 (25mg/d) hours (day 11) Sator et al. Gyn End 2013;29: cyclodextrin de Ziegler et al. Fertil Steril 2013

26 AEs/Nb of injections (%) New self-injectable P4 (25mg/d) ,00 60,00 50,00 40,00 30,00 20,00 10,00 0,00 Injection site bruising AEs related to study drug: Nb of AEs recorded durigng the 14 days of treatment /tot Nb of injections per group (%) Injection site erythema Injection site redness Injection site swelling tolerability Prog IBSA 50 mg IM Oily Prog 50 mg IM Other Sator et al. Gyn End 2013;29: Total cyclodextrin de Ziegler et al. Fertil Steril 2013

27 Physiology: production of progesterone = 25 mg/day

28 Physiology: production of progesterone = 25 mg/day

29 Physiology: production of progesterone = 25 mg/day P4: pulsatile production under the control of LH: LH Day LH +10 5ng/mL P4

30 Luteal phase support (LPS):

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32

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34 Prolutex Crinone

35 The needs for LPS The options existing and doses used A sub-cutaneous P4 preparation Non-pelvic effects of P4?

36 Luteal phase support (LPS):

37 Luteal phase support (LPS):

38 P < IM P4 Crinone

39 There appears to be a superiority of IM over vaginal progesterone for frozen embryo transfers (FET) The difference may result from non-pelvic effects of progesterone (immuno-suppression and/or Vasopressin/oxytocin)

40 LPS is necessary in ART because CL support by LH is deficient Progesterone production during the luteal phase is of ~25ng/mL A new sub cutaneous progesterone preparation is available: Prolutex (25mg/day) Endometrial effects of vag and injectable progesterone are equivalent. In FET, injectable progesterone results in higehr PR possibly, through non-pelvic effects.

41 Charlers Chapron Bruno Borghese Hervé Foulot Amin Bititi Paul Mazurk Guillaume Pierre Marie Christine Lafay Fouzia Decupere François X. Aubriot Dominique de Ziegler Vanessa Gayet Pietro Santulli Rebecca Monffat Paul Pitrea Corine Menez Bander Kuttbi Ann Marszalek Alessandra Fubini

42 Physiology: production of progesterone = 25 mg/day P4: pulsatile production under the control of LH: LH Day LH +8 P4

43 Luteal phase support (LPS):

44 Luteal phase support (LPS):